People who are infected with HIV, especially those on long-term antiretroviral therapy (ART) or who use cocaine, have a high prevalence of LV dysfunction. Since ART use could lead to diabetes, and since cardiac steatosis (fatty heart) has been identified in those with diabetes, it is critical to examine whether HIV infection, ART use, and cocaine use promote cardiac steatosis, a marker for cardiomyopathy. Virtually no reported studies have addressed the combined effects of HIV infection, ART use, and cocaine use on the etiology of cardiomyopathy. According to our preliminary study, cardiac steatosis is prevalent in HIV-infected individuals, especially those on ART. These results are entirely new and never before reported. This application seeks support for conducting novel research on the effects of HIV infection, ART use, and cocaine use on cardiac steatosis. The proposed study, using the cohort of study participants enrolled in the ongoing study DA12777, will employ magnetic resonance imaging (MRI) to accurately quantify the ectopic fat deposition in the myocardium and will explore the association between HIV infection, ART use, cocaine use, and cardiac steatosis. The proposed specific aims of this study are (1) To estimate the prevalence and incidence of cardiac steatosis and left ventricular (LV) dysfunction in cardiovascularly asymptomatic men and women with one of the following characteristics: HIV(-) and cocaine(-); HIV(-) and cocaine(+); HIV(+) and cocaine(-) and ART(-); HIV(+) and cocaine(-) and ART(+); HIV(+) and cocaine(+) and ART(-); and HIV(+) and cocaine(+) and ART(+); (2) To examine the effects of HIV infection on the presence and development of cardiac steatosis and regional LV dysfunction; (3) To examine the effects of the various classes of ART and individual ART on the presence and development of cardiac steatosis and regional LV dysfunction in HIV-infected persons; (4) To examine the effects of cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction; (5) To examine the joint effects of HIV infection, ART use, and cocaine use on the presence and development of cardiac steatosis and regional LV dysfunction; and (6) To investigate the direct effects and mechanisms of HIV infection, ART use, and cocaine use on mitochondrial damage. This study will be among the first, if not the very first, to explore the mechanisms of premature HIV/cocaine-related cardiomyopathy, and its findings may lead to a breakthrough in research on prevention/intervention related to heart failure in HIV-infected persons and to translation of scientific discoveries into clinical applications. PUBLIC HEALTH RELEVANCE: This study will investigate why HIV-infected African Americans have high rates of cardiac steatosis and regional left ventricular dysfunction. The study could provide critical information for understanding the mechanisms of premature heart failure and lead to a breakthrough in research on prevention/intervention of heart disease in HIV-infected persons and to translation of scientific discoveries into clinical applications.